Obesity Expands a Distinct Population of T Cells in Adipose Tissue and Increases Vulnerability to Infection

Abstract

Summary: Obesity in humans is associated with poorer health outcomes after infections compared with non-obese individuals. Here, we examined the effects of white adipose tissue and obesity on T cell responses to viral infection in mice. We show that lymphocytic choriomeningitis virus (LCMV) grows to high titer in adipose tissue. Virus-specific T cells enter the adipose tissue to resolve infection but then remain as a memory population distinct from memory T cells in lymphoid tissues. Memory T cells in adipose tissue are abundant in lean mice, and diet-induced obesity further increases memory T cell number in adipose tissue and spleen. Upon re-challenge infection, memory T cells rapidly cause severe pathogenesis, leading to increases in lipase levels, calcification of adipose tissue, pancreatitis, and reduced survival in obese mice but not lean mice. Thus, obesity leads to a unique form of viral pathogenesis involving memory T cell-dependent adipocyte destruction and damage to other tissues. : Obesity is associated with increased morbidity and mortality after viral infections. Using a mouse model of obesity, Misumi et al. identify a distinct population of memory T cells in white adipose tissue and a memory cell-dependent pathogenic response to infection that leads to acute fat necrosis, pancreatitis, and lethality. Keywords: T cell memory, obesity, white adipose tissue, pancreatitis, LCMV, tissue-resident memory T cells, Trm